title: A polymorphism in the TYMP gene is associated with the outcome of HLA-identical sibling allogeneic stem cell transplantation.
abstract: Thymidine phosphorylase (TYMP), an enzyme involved in nucleotide synthesis, has been implicated in critical biological processes such as DNA replication, protection against mutations, and tissue repair. In this work, we retrospectively evaluated the influence of a polymorphism in the TYMP gene (rs112723255; G/A) upon the outcome of 448 patients subjected to allogeneic stem cell transplantation (allo-SCT) from an human leukocyte antigen (HLA)-identical sibling donor. The TYMP genotype of patients correlated with overall survival-carriers of the minor allele (A) being at an increased risk of dying after transplantation (hazard ratio, HR = 1.9; P = 0.004). This effect was mostly due to differences in transplant toxicity-related mortality (HR = 2.5; P = 0.029). In addition, the TYMP genotype of donors was associated with the risk of chronic graft-versus-host disease (GVHD)-carriers of the minor allele being at an increased risk of developing this complication ([HR] = 1.7; P = 0.039). The impact of such polymorphism on the risk of chronic GVHD is limited to patients transplanted in early stage disease (HR = 2.2; P = 0.019). The combination of a donor harboring the minor allele with a patient homozygous for the major allele was associated with the highest risk of chronic GVHD (HR = 2.8; P = 0.008). These findings provide the first evidence of the significant impact of the TYMP genotype upon the clinical outcome of patients treated with HLA-identical sibling allo-SCT.
authors.affiliation: Department of Hematology and Medical Oncology, Hospital Clínico Universitario de Valencia, Instituto de Investigación Sanitaria INCLIVA, Universitat de Valencia, Valencia, Spain.
authors.forename: Vicent
authors.initials: V
authors.lastname: Guillem
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Hernández-Boluda
authors.forename: David
authors.initials: D
authors.lastname: Gallardo
authors.forename: Ismael
authors.initials: I
authors.lastname: Buño
authors.forename: Anna
authors.initials: A
authors.lastname: Bosch
authors.forename: Carolina
authors.initials: C
authors.lastname: Martínez-Laperche
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Cámara
authors.forename: Salut
authors.initials: S
authors.lastname: Brunet
authors.forename: Carmen
authors.initials: C
authors.lastname: Martin
authors.forename: José B
authors.initials: JB
authors.lastname: Nieto
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Ariadna
authors.initials: A
authors.lastname: Pérez
authors.forename: Juan
authors.initials: J
authors.lastname: Montoro
authors.forename: Ana
authors.initials: A
authors.lastname: Garcia-Noblejas
authors.forename: Carlos
authors.initials: C
authors.lastname: Solano
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000209:etiology / Q000235:genetics / Q000401:mortality; D019337:Hematologic Neoplasms / Q000235:genetics / Q000401:mortality / Q000628:therapy; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012307:Risk Factors; D035781:Siblings; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013939:Thymidine Phosphorylase / Q000235:genetics*; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: C543750:TYMP protein, human; D013939:Thymidine Phosphorylase